Acquired Immunodeficiency Syndrome (AIDS) was first reported in the United States in 1981 and the AIDS epidemic shows great diversity in severity and timing worldwide. Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, is a retrovirus composed of RNA genetic material, which inhibits the human immune system from fighting off infection. Currently known anti-HIV agents fall into four major categories: (1) nucleoside reverse transcriptase inhibitors; (2) non-nucleoside reverse transcriptase inhibitors; (3) protease inhibitors; and (4) ribonucleotide reductase inhibitors (De Clercq et al. Rev. Med. Virol. (2000), 10, 255). The first clinically used drug for the treatment of HIV is azidothymidine (AZT) (Ezzell et al. Nature, (1987), 329, 751). AZT exerts its function by incorporating into the DNA chain, and results in interrupting chain elongation and impeding further replication of the genome (http://www.aids.org/). Although AZT and its cocktail regimens have shown promising effects on suppression of HIV-1 replication, drug-resistant HIV-1 as well as antiretroviral toxicity are still causes of growing clinical and public concern (Deeks S. G. Lancet (2003), 362, 2002).
The medicinal properties of metal-based compounds have been and continued to be an area of interest in new drug discovery (Orvig et al. Chem. Rev. (1999), 99, 2201-2203; Abrams et al. Science (1993), 261, 725-730). In the literatures, metal-based compounds have demonstrated clinical applications with the most notable example being cisplatin (Rosenberg et al. Nature (1969), 222, 385-386). While there have been extensive research on cytotoxic metal compounds, related studies on anti-viral metal-based compounds are under development. To our knowledge, there are several classes of metal-based compounds such as polyoxometalates (Rhule et al. Chem. Rev. (1998), 98, 327-357; Hill et al. J. Med. Chem. (1990), 33, 2767-2772), metallocyclams (Liang et al. Chem. Soc. Rev. (2004), 33, 246-266), vanadyl (Wong et al. Chem. Commun. (2005), 3544-3546), zinc (Aoki et al. Chem. Rev. (2004), 104, 769-787), and gold (Sun et al. ChemBioChem (2004), 5, 1293-1298) complexes known to display notable anti-HIV activities. However, examples regarding to the anti-viral activities of ruthenium-based compounds are limited (Luedtke et al. ChemBioChem (2002), 3, 766-771; Mishra et al. Bioorg. Med. Chem. (2001), 9, 1667-1671).